PROJECT SUMMARY/ABSTRACT The Stanford University High-Throughput Bioscience Center (HTBC) is proposing to purchase an Automated High-Content Confocal Imaging System to replace a >10 year old non-confocal imager. The HTBC is a core facility in the Stanford University School of Medicine that performs high-throughput screening (HTS) and high-content screening (HCS). The main component of the requested system is a Molecular Devices ImageXpress Micro (IXM) Confocal high-content imaging microscope. This microscope will be integrated to microplate stackers and an existing Thermo Cytomat 2C automated incubator via a new Thermo Spinnaker robotic arm. A new-quad processor Dell server will also be purchased to allow for rapid on-the-fly image data analysis as well as image storage and backup. The proposed instrumentation would significantly enhance the HTBC's capabilities by not only increasing the efficiency, speed and resolution of high- content imaging, but also allow for much more advanced modes of imaging including 3D confocal imaging. Currently, HTBC's original non-confocal ImageXpress Micro has the ability to perform 1) time-lapse widefield epi-fluorescence imaging with environmental control on a single microplate, or 2) automated widefield epi-fluorescence or brightfield imaging without environmental control on multiple live-cell or fixed plates. The IXM Confocal with robotic integration adds the ability to perform these types of imaging all- inclusive and fully automated with environmental control, fluidics and the added ability of confocal 3D imaging. The IXM Confocal along with the HTBC's compound and RNA interference screening libraries will allow Stanford researchers to stay at the forefront of drug discovery by adding the ability to screen whole organisms and cultured spheroids and organoids in a robust automated high-throughput manner. Overall, this instrumentation will significantly advance scientific discovery and innovation on our campus and will advance our understanding of human health and disease and lead to the discovery of new targeted drug therapies important for personalized medicine.